title: Differential analgesic effects of morphine and gabapentin on behavioural measures of pain and disability in a model of osteoarthritis pain in rats.
abstract: Osteoarthritis (OA) is associated with chronic debilitating joint pain. Pain is the result of an emotional and sensory experience and preclinical models of OA can thus be useful to better understand the underlying mechanisms of the disease and test new therapeutic options. We induced unilateral knee OA in Sprague-Dawley rats using monosodium iodoacetate (MIA), a glycolysis inhibitor and assessed the effects of acute and chronic morphine and gabapentin using a battery of quantitative behavioural outcome measures of pain and disability. Animals received a single intra-articular injection of 2mg MIA in 25 microl saline, causing inflammation and progressive cartilage degradation. Mechanical and thermal sensitivity as well as ambulatory-evoked pain were then monitored using von Frey hairs, acetone and a rotarod. Once maximum nociceptive responses were reached, chronic bi-daily morphine (3mg/kg s.c.) or gabapentin (30 mg/kg s.c.) were administered for 5 days. We observed a marked biphasic mechanical hypersensitivity that increased and reached a plateau from day 14 (317.6% of control response, p<0.01, with von Frey 6g). Moreover we found a marked cooling hypersensitivity, and validated a novel ambulatory-evoked pain score. These measures were significantly reduced after both acute (13.3% of sham response, p<0.01, von Frey 6g) and chronic (38.3%, p<0.05) morphine whilst only chronic gabapentin (37.0%, p<0.05) had an effect. We show the reliability of the model in terms of mechanical hypersensitivity and demonstrate cooling hypersensitivity and ambulatory-evoked pain. In terms of translational research, the effects of morphine and gabapentin validate the model and suggest trials of these therapeutic approaches in OA patients.
authors.affiliation: University College London, Neuroscience, Physiology and Pharmacology, London WC1E 6BT, UK. j.vonsy@ucl.ac.uk
authors.forename: Jean Laurent
authors.initials: JL
authors.lastname: Vonsy
authors.forename: Javid
authors.initials: J
authors.lastname: Ghandehari
authors.forename: Anthony Henry
authors.initials: AH
authors.lastname: Dickenson
mesh_terms: D000588:Amines / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003080:Cold Temperature; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D000077206:Gabapentin; D007461:Iodoacetates; D008124:Locomotion / Q000502:physiology; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D009068:Movement / Q000502:physiology; D010003:Osteoarthritis / Q000150:complications* / Q000188:drug therapy / Q000523:psychology*; D010146:Pain / Q000188:drug therapy / Q000209:etiology* / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use*
chemical_list: D000588:Amines; D000700:Analgesics; D000701:Analgesics, Opioid; D003509:Cyclohexanecarboxylic Acids; D007461:Iodoacetates; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine